ArticleArteriosclerosis, thrombosis, and vascular biology2013
Inflammatory cytokines promote mesenchymal transformation in embryonic and adult valve endothelial cells.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 225 citations in OpenAlex.
- miR-483 Targeting of CTGF Suppresses Endothelial-to-Mesenchymal Transition: Therapeutic Implications in Kawasaki Disease.Circulation research · 2017Trial
- Cyclic stretch inhibits cell invasion in 3D scaffolds.bioRxiv : the preprint server for biology · 2026Article
- Endothelial-to-Mesenchymal Transition Mechanisms in Vascular Remodeling of Pulmonary Hypertension.International journal of molecular sciences · 2026Review
- Human Plasma in Calcific Aortic Valve Disease: Not Simply a Depot of Biomarkers.Journal of the American Heart Association · 2026Article
- Oscillatory shear stress-driven endothelial-to-mesenchymal transition: a critical mechanical signal transduction mechanism in atherosclerosis progression.Cell death discovery · 2026Review
- Endothelial to mesenchymal transition in cardiovascular diseases: molecular insights and clinical perspectives.European heart journal · 2026Review
- Intracavernous Injection of Mechanically Extracted Stromal Vascular Fragments Suppresses Endothelial-Mesenchymal Transformation to Mitigate Erectile Dysfunction in Hypertensive Rats.Stem cells international · 2026Article
- Circulating cytokines as triggers of endothelial dysfunction and sex-specific interstitial cell response in fibrocalcific aortic valve disease.International journal of biological sciences · 2026Article
- Purinergic signaling modulates endothelial-to-mesenchymal transition in human aortic valve endothelial cells.BBA advances · 2026Article
- NRG1 Suppresses NLRP3 Inflammasome Activation and Endothelial-Mesenchymal Transition in Cerebral Ischemia-Reperfusion Injury: Association with the AKT/NF-κB Pathway.Journal of inflammation research · 2026Article
- IGF1-mediated mesenchymal-endothelial transition as a potential regulatory target in calcific aortic valve disease.BMC medicine · 2025Article
- COL8A1 regulates endothelial phenotype in inflammatory endothelial-to-mesenchymal transition.American journal of physiology. Heart and circulatory physiology · 2025Article
- Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies.Journal of advanced research · 2025Review
- Unveiling the secret of cellular metamorphosis: the crucial role of EndMT mechanisms in COVID-19-induced pulmonary fibrosis.Inflammopharmacology · 2025Review
- Article
- Shifting Shapes: The Endothelial-to-Mesenchymal Transition as a Driver for Cancer Progression.International journal of molecular sciences · 2025Review
- Telomere Length and Clonal Hematopoiesis of Indeterminate Potential: A Loop Between Two Key Players in Aortic Valve Disease?Journal of cardiovascular development and disease · 2025Review
- Maternal Immune Activation: Implications for Congenital Heart Defects.Clinical reviews in allergy & immunology · 2025Review
- Mechanistic insights and emerging therapeutic strategies targeting endothelial dysfunction in cardiovascular diseases.Archives of pharmacal research · 2025Review
- Involvement of USP7 in aggravating Kawasaki disease by promoting TGFβ2 signaling mediated endothelial-mesenchymal transition and coronary artery remodeling.International immunopharmacology · 2025Article
80 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveInflammatory activation of valve endothelium is an early phase of aortic valve disease pathogenesis, but subsequent mechanisms are poorly understood. Adult valve endothelial cells retain the developmental ability to undergo endothelial-to-mesenchymal transformation (EndMT), but a biological role has not been established. Here, we test whether and how inflammatory cytokines (tumor necrosis factor-α and interleukin-6) regulate EndMT in embryonic and adult valve endothelium. METHODS AND
resultsUsing in vitro 3-dimensional collagen gel culture assays with primary cells, we determined that interleukin-6 and tumor necrosis factor-α induce EndMT and cell invasion in dose-dependent manners. Inflammatory-EndMT occurred through an Akt/nuclear factor-κB-dependent pathway in both adult and embryonic stages. In embryonic valves, inflammatory-EndMT required canonical transforming growth factor-β signaling through activin receptor-like kinases 2 and 5 to drive EndMT. In adult valve endothelium, however, inflammatory-induced EndMT still occurred when activin receptor-like kinases 2 and 5 signaling was blocked. Inflammatory receptor gene expression was significantly upregulated in vivo during embryonic valve maturation. Endothelial-derived mesenchymal cells expressing activated nuclear factor-κB were found distal to calcific lesions in diseased human aortic valves.
conclusionsInflammatory cytokine-induced EndMT in valve endothelium is present in both embryonic and adult stages, acting through Akt/nuclear factor-κB, but differently using transforming growth factor-β signaling. Molecular signatures of valve EndMT may be important diagnostic and therapeutic targets in early valve disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.